This investigation is concerned with the biologic basis at the cellular and molecular levels for cardiomyopathy associated with the use of chemotherapeutic agents, adriamycin and related anthracycline analogs. The drugs appear promising in the treatment of several malignancies; however, maintenance therapy may be contraindicated because of cumulative cardiotoxicity of unknown etiology. Mammalian myocardial cells in culture are used as a model system and selected cell processes are studied in cells treated with adriamycin or related drugs in an attempt to localize the site and the mechanism of action. The antimitotic activity of the drugs may involve the intercalation into DNA, but it is not clear what the mechanism is in cardiotoxicity since adult myocardium is not characterized by fast proliferating cells. The effect of adriamycin on the rate and extent of replicative DNA synthesis as opposed to unscheduled DNA synthesis and the effect upon the fidelity of DNA synthesis in treated cells will be determined under a variety of culture conditions. The effect on gene expression in terms of specific proteins of the differentiated myocardium, myosin and creatine kinase, the two enzymes involved in the contractile function and in the associated energy production, respectively, will be investigated. The myocardial culture permits a direct testing of a hitherto unresolved problem of a possible effect of adriamycin on cellular energy production as a cause of cardiotoxicity and associated with it the effects on Ca2 ion transport system in the myocardium. The information generated from this study will be of importance in elucidating the mechanism of action of the drugs and their usefulness in maintenance therapy. Furthermore, it could add to the elucidation of the poorly understood primary myocardiopathies.